1. Field of the Invention
The present invention relates to methods and apparatus for determining cardiac output, the amount of blood the heart is pumping, as well as identifying pulmonary functions, without resorting to invasive techniques which introduce foreign objects and the like, into a body.
2. Description of the Related Art
Monitoring the cardiovascular system to determine myocardial performance is of paramount importance in patient care, regardless of whether the patient is located in the physician""s office, emergency or operating room, intensive care unit, at an accident scene or in transit (e.g., in an ambulance). Although routine cardiac monitoring usually begins with a determination of the patient""s heart/pulse rate and blood pressure, in the case of patients who are experiencing cardiac difficulties or distress, additional diagnostic details regarding the operation of the heart are needed. Such additional monitoring may quickly progress to include an electrocardiogram (EKG) and the measurement of hemodynamic variables such as cardiac output.
The term cardiac output is defined as the mean or average total blood flow in the circulatory system per unit time. Cardiac output is associated with the strength of the heart and is consequently an important parameter in assessing the condition of a patient""s health. Knowledge of cardiac output level and trends have important diagnostic value in that they provide the clinician with information to help him/her assess how well the myocardium is functioning so as to provide the basis for the timely delivery and prescription of appropriate therapeutic modalities. Pulmonary function relates to the ability of the body to make use of oxygen and to eliminate wastes such as carbon dioxide. This parameter is strongly affected by physiological conditions such as deadspace and shunts, and the ability to quantify these conditions forms a major part of cardiopulmonary therapy.
Owing to the uncertainties of the geometry of blood vessels (e.g., diameter, compliance, etc.) and the dynamic nature of the heart itself, conventional flowmetering techniques such as flow resistance measurement or velocity (e.g., Doppler and ultrasonic) measurements have proven unreliable in estimating cardiac output. As a result, cardiac output is routinely measured invasively; that is, by surgically placing an instrument into the arteries near the heart.
The current state-of-the-art, and arguably the xe2x80x9cgold standardxe2x80x9d for cardiac output measurement, is considered to be either the Direct Fick or thermodilution technique using a flow-directed catheter (Swan-Ganz catheter). The catheter is physically threaded through a large vein (femoral, internal jugular, etc.) into and through the right atrium and right ventricle of the heart into the pulmonary artery located between the heart and the lungs. At that point, thermal dilution techniques may be used to quantify the blood flow. Unfortunately, because of the invasive nature of the technique, the potential risk to the patient of hemorrhage, dysrhythmia or cardiac arrest is relatively high. Consequently, the routine use of invasive techniques such as thermal dilution to measure cardiac output is presently limited to specific clinical situations where the benefits far outweigh the risks.
A significant number of patients (as many as two percent) do not survive the surgery associated with the catheter insertion procedure itself. Hence, this technique is limited to those situations where patients are extremely ill and the increased risk for increased morbidity and mortality is acceptable. Efficacy studies in recent medical literature report data that raises questions as to the risk-benefit ratio of the information provided by invasive cardiac output measurement and whether invasive cardiac output measurement is in the best interest of the patient. In addition to the intrinsic danger of the invasive procedure, the monetary cost of the procedure is relatively high, as it is in itself a surgical procedure and, as with almost all surgical procedures, its hands-on labor intensity by expensive medical personnel results in high costs. It is estimated that nearly $200 million is spent in the U.S. alone for invasive cardiac procedures, equipment and materials, and recent medical literature also questions the cost effectiveness of these invasive techniques.
Adding to the increasing concern that the cost-benefit ratios may not be in the patient""s best interest is the fact that many patients may not be adequately monitored and consequently are being put at risk from lack of diagnostic information. Presently, no reliable, accepted, cost-effective, non-invasive techniques are available for continuous monitoring; thus, only the sickest and highest risk patients are candidates for continuous cardiac monitoring. This leaves a huge population that goes unmonitored, of which it is well known that significant numbers encounter cardiac distress of one kind or another during non-cardiac-related procedures. There are many clinical situations such as most routine surgery/anesthesia, outpatient care, emergency medicine, and home care where monitoring cardiac output is not routine, but if it were, would be of significant benefit to patient care. There are significant complications that require treatment, many of which may have been prevented had myocardial function monitoring been available and appropriate responses initiated. Current estimates of the costs of aftercare treatment for such cardiac complications exceed $22 billion in the U.S. alone.
Non-invasive and less invasive techniques are therefore highly desirable. Unfortunately, because of the variability and complexity of the physiology of the circulatory system and the pathology of disease, no currently used non-invasive or less-invasive methodologies are known to be capable of obtaining reliable cardiac output values. Although less-invasive methodologies such as impedance cardiography, Doppler-shift techniques, and non-invasive rebreathing and single-breath Fick techniques are or have been available commercially to measure cardiac output, in their current implementations, they all suffer from significant problems and/or disadvantages. In general, all of these techniques are extremely expensive, require a highly trained technical staff, and are limited to a few well-defined clinical situations. In addition, each technique has unique specific limitations.
More particularly, impedance cardiography requires the correct placement of electrodes on the neck and abdomen that are excited by a high frequency (e.g., 100 kHz) current and the subsequent monitoring of the resulting impedance changes between the electrodes. The impedance changes of the chest are used to determine the cardiac stroke volume resulting from the expansion and contraction of the cardiac volume. Cardiac output can be calculated by combining this volume with heart rate in an appropriate algorithm. The limitations of this technique include: the need/ability to correctly place the electrodes, accurate accounting for the volume changes resulting from the inhalation and exhalation of the lungs, and patient movement. Furthermore, the high impedance electrodes act as antennas that pick up considerable amounts of electromagnetic interference (EMI), thereby interfering with the measurements.
The Doppler-shift technique is based on the effect of the shift in frequency of sound from a stationary source that is reflected by a moving object. With this method, the average velocity of the blood flowing in an artery can be readily measured. However, to determine the volumetric flowrate, the cross-sectional area of the artery must be known. Obviously, soft tissue visualization techniques such as MRI are not practical at this time for general use, and ultrasound imaging generally tends not to be accurate enough, although it is used to provide a relative measure in some applications such as transesophageal-echocardiography. Costs are prohibitively high, and in this age of managed care cannot be considered practical for routine use. Esophageal Doppler techniques are also plagued with inevitable patient motion artifacts.
A variety of indirect Fick techniques, including breath holding, single breath and rebreathing, have been proposed over the years to estimate cardiac output from various measurements of respired and tracer gasses. Breath holding and single-breath techniques using tracer gasses have had limited success but are not suited to continuous monitoring. A single-breath technique proposed by Kim et al. in xe2x80x9cEstimation of true venous and arterial PCO2 By Gas Analysis of a Single Breath,xe2x80x9d J. Appl. Physiol., Vol. 21, No. 4, pp. 1338-1344, (1966), incorporated herein by reference in its entirety, probably had the greatest potential because of the promise of breath-by-breath monitoring. However, general acceptance has been lacking due to technology limitations for precise, real time, simultaneous respiratory gas measurements and limited experimental validation of their underlying assumptions.
Perhaps most popular and most widely accepted of the indirect Fick techniques have been CO2 rebreathing techniques. Presently, the only commercially available non-invasive device is the Novametrix Non-Invasive Cardiac Output (NICO) monitor, which monitors respired carbon dioxide production combined with partial rebreathing (inhaling air with elevated carbon dioxide levels) in a variation on the well-known Fick Principle. (The Fick Principle relates essentially to a statement of flow continuity and mass balance over the cardiovascular system.) More specifically, a non-dispersive infrared CO2 sensor and a venturi-type flowmeter measure the CO2 concentration and respired volumetric flowrate and hence CO2 production. The Fick equation is used to calculate cardiac output as the ratio of the carbon dioxide produced to the arteriovenous difference of carbon dioxide content in blood. NICO is reported to have reasonable correlation with direct Fick and indicator dilution measurements in patients with normal, healthy lungs with minimal deadspace and/or no pulmonary shunts.
However, the NICO system""s reliance on the products of metabolism (i.e., the Novametrix sensors can measure only carbon dioxide) results in questionable accuracy in the presence of shunts and deadspace in the lungs; the accuracy of the NICO system is also compromised because it must rely on compensatory algorithms that are highly dependent on physiological conditions and unknown metabolic and respiratory parameters. Consequently, results are poor for patients with pulmonary and/or obstructive airway disease due to the effects of V/Q mismatching caused by increased pulmonary shunts and deadspace. These effects invalidate the assumption that PeCO2 can be used to approximate the values for PvCO2 and PaCO2. The dilutional effects of a significant shunt on the pulmonary capillary blood flow invalidate the assumption that systemic cardiac output is equal to pulmonary capillary blood flow. Reasonable success has been achieved in compensating for shunts by measuring the degree of O2 saturation in a peripheral artery with a pulse oximeter. The major disadvantages of this technique are: bulk of the rebreathing apparatus and the time required to collect the data to calculate cardiac output. This latter disadvantage precludes the use of this device for continuous, or even breath-by-breath monitoring; consequently, dynamic changes may not be detected quickly enough for preventive measures to be taken. Furthermore, since the rebreathing may take longer than a recirculation time, readings may be affected by accumulated CO2.
While monitors for the continuous, breath-by-breath, measurement of CO2, O2, and anesthetic agents are commercially available, all are lacking in one or all of the following attributes: reliability, ease of operation, accuracy, the need for calibration, small size, and low acquisition cost and life-cycle cost. For example, CO2 monitors using non-dispersive IR spectroscopy can cost over $1000 for hand-held versions and as much as $20,000 (with additional high life-cycle costs associated with the periodic calibration and maintenance of the equipment) for a full-spectrum operating room gas monitoring. Mass spectroscopy and Raman scattering systems are even more costly and bulky. In addition to cost, physical size, and inconvenience of operation (calibration) conventional systems have found limited use of gas monitoring in the field for such things as validation of endotracheal (ET) tube placement during emergency intubation and patient transport. Extubation, leading to severe, irreversible consequences, frequently occurs during patient transport, yet no monitors meeting the above characteristics have been available.
Consequently, there remains a need for a reliable, cost-effective, non-invasive cardiac output monitoring system capable of continuously measuring cardiac output and pulmonary function on a breath-by-breath basis using measurements of inspired and respired gasses. The availability of cardiac output measurement to routinely monitor the large population currently without benefit of such monitoring could significantly reduce the huge aftercare costs and morbidity and mortality resulting from undiagnosed cardiac complications in non-cardiac-related procedures. A lightweight, rugged device would be ideally suited for use in field environments such as the ambulance and MEDEVAC transport, as well as the doctor""s office, clinic, emergency and operating rooms and in intensive care units (ICU).
Since there is no currently acceptable noninvasive cardiac output monitor available for routine use, there remains a need for a technique to accurately measure cardiac output and eliminate risk of infection or invasive trauma to the patient. Further, any technique that is economical, reliable, accurate, and simple to operate and maintain becomes a candidate for routine utilization. Moreover, a device that is lightweight and small, opens the market to ambulatory monitoring, sports and physical fitness, and home care of cardiac patients. Finally, such a device would complement rural and military telemedicine where remotely located specialists can diagnose and treat patients given sufficient patient data.
Therefore, in light of the above, and for other reasons that become apparent when the invention is fully described, an object of the present invention is to provide a non-invasive cardiac output monitoring system that uses measurements of inspired and respired gasses in the determination of cardiac output.
It is another object of the present invention to utilize a mathematical model of the human physiology that will compensate for variations in physical and disease states in determining cardiac output from respired gasses.
It is a further object of the present invention to measure uptake and release of inert and/or insoluble indicator gasses that are not metabolized and absorbed in order to eliminate the vagaries of the metabolic and absorption processes in determining cardiac output.
It is yet a further object of the present invention to use a gas analyzer that measures or assays all the gasses that are inhaled and respired, not just an indicator gas alone, thereby allowing for a complete description of the uptake, distribution and release of the gasses, that then allows for accurate inputs to the physiological model.
It is still a further object of the present invention to provide for a very low cost implementation of the technology in order to promote widespread use and to improve the general standards of care for patients.
It is another object of the present invention to measure, in a real time, breath-by-breath situation, oxygen and carbon dioxide concentration from which both mixed venous and arterial concentrations of carbon dioxide can be determined.
Another object of the present invention is to measure on a real time, breath-by-breath basis the anatomical and physiological deadspace of the lungs by combining breathing mass flow measurement with concentration waveform analysis.
Still another object of the present invention is to provide a low cost means for determining the cardiac output and pulmonary function of a human being on a breath-by-breath basis while accurately accounting for disease states as well as physical conditions.
Yet another object of the present invention is to provide a cardiac output monitoring device that measures attributes of respired gasses on a breath-by-breath basis, which measurements can be used with any of the known Fick techniques for determining cardiac output non-invasively.
A fundamental aspect of the present invention is the use of a respired gas analyzer that is capable of simultaneously quantifying the concentrations of several gasses in real time and a true, real time mass flowmeter to calculate uptake, production and expiration of gasses to provide measurements with known relationships to cardiac output and pulmonary function. A gas analyzer suitable for use in the present invention is disclosed in pending U.S. patent application Ser. No. 09/104,997 entitled xe2x80x9cMethod and Apparatus For Real Time Gas Analysisxe2x80x9d filed Jun. 26, 1998 by Tadeusz M. Drzewiecki, and a pending provisional U.S. patent application Ser. No. 60/121,370 entitled xe2x80x9cMethods and Apparatus for Real Time Fluid Analysisxe2x80x9d filed Feb. 25, 1999 by the same inventor. The subject matter disclosed in those applications is incorporated herein by reference in its entirety.
The combination of a real time mass flowmeter and an inexpensive gas analyzer capable of simultaneously determining concentrations of multiple gasses in real time permits for the first time accurate determination of cardiac output on a breath-by-breath basis from analysis of respired gasses. More particularly, the cardiac output monitoring system of the present invention can be used with any of the Fick-principle-based non-invasive techniques that have been proposed in the art for measuring cardiac output from respired gasses, but that have heretofore been impractical, prohibitively expensive, inaccurate and/or unreliable. Moreover, the parameters measured and the extensive information provided in real time by the cardiac output monitoring system of the present invention allow known techniques to be refined and extended to more accurately account for pulmonary factors such as shunts and deadspace in the determination of cardiac output.
The gas analyzer disclosed in the aforementioned Drzewiecki patent applications simultaneously and in real time assays gasses, allowing accurate quantification of all the constituents of respiratory gas mixtures. Because the gas analyzer measures physical properties of a gas mixture, including density and viscosity, a conventional flowmeter can be compensated for changes in gas properties, not only as a function of temperature but also for changes in composition. This allows the use of any one of a variety of low cost pressure-drop-type (fixed or variable orifice) flowmeters to accurately measure respired flows over a wide range of gas compositions, with equivalent accuracy of expensive mass flowmeters. Thus, artifacts caused by breathing in products of combustion or other gasses (e.g., anesthetics) that would affect the computation of gas uptake/production by giving erroneous volumetric or mass flows are eliminated. In this manner, the volumetric gain or loss from the lungs can be quantified throughout the respiratory cycle to provide the necessary data to accurately calculate cardiac output using the Fick Principle. By overcoming the technical difficulty of measuring the concentrations of oxygen and carbon dioxide simultaneously (with standard errors that cancel rather than add as they do with independent sensors) an accurate measure of cardiac output can be obtained using single-breath techniques, such as that disclosed by Kim. Furthermore, by providing an improved methodology for estimating alveolar CO2 and O2 concentration values that includes the effects of physiological (including alveolar) deadspace, by using the Bohr equation combined with the considerable work of Fletcher on analyzing CO2-volume waveforms, in combination with an iterative anatomical/physiological model of gas exchange that converges on measured expiratory gas concentrations, the Kim technique provides accurate results under significantly broader conditions to include exercise and disease states. Finally, by including a pulse oximeter to measure O2 saturation, pulmonary shunts can be compensated for directly in the expression derived for the O2 tension rather than by trying to estimate a value for shunts directly and thereby adjust the CO2 values.
The cardiac output monitor of the present invention poses essentially no risk to the patient, is easy to use, is inexpensive to manufacture and has virtually no low life-cycle costs (e.g., no recalibration is ever required), thereby making it economical to operate, and can be sized and packaged to be handheld while maintaining an instrument (e.g., waveforms, etc.) level output capability.
By measuring physical properties such as density, viscosity and specific heat with very simple but highly precise pressure, flow, temperature and frequency transducers, the assay of the constituent concentrations is precisely calculated. The unique combination of concentrations that make up a gas mixture with given measured properties (viscosity, density, specific heat) is determined by deconvolving the fundamental relationships that define mixture property values in terms of their constituent concentrations. State-of-the-art, low cost, ultra-high dynamic range, microelectromechanical system (MEMS) pressure transducers, and a highly precise platinum RTD temperature sensor integrated with a specially designed fluidic oscillator flowmeter, measure the pressure drop, temperature and flow in a microfluidic capillary viscometer, orifice densitometer, and sonic microcalorimeter (specific heat sensor) integrated on a precision micro-injection molded Laboratory-on-a-Chip (LOAC). A high-speed microprocessor provides solutions to the governing equations and drives an LCD. Because the concentrations are determined from physical first principles, the gas analyzer never requires calibration or maintenance, which is a major advantage for field-use devices.
According to one embodiment of the present invention, a known amount of an essentially inert, insoluble, indicator gas is tracked during respiration. The input parameters (cardiac output, deadspace, shunts) to a validated physiological model (software) are iterated to obtain a matching time-history of the released (exhaled) indicator gas. The use of a model that allows for individual variations and disease states, as well as variations in body mass and uptake and distribution parameters, results in a credible as well as accurate output, that, because it matches the measured values, represents a reasonable estimate of the parameters. The values of cardiac output, shunts and deadspace that match the measured values are thus among the outputs of the monitoring system of the present invention.
In another, more general embodiment of the present invention, the use of a tracer gas is dispensed with and the analysis of the consumed oxygen and produced carbon dioxide and their concentration waveforms is used to provide a measure of the mixed venous and arterial concentrations of carbon dioxide and a measure of the anatomical and physiological deadspace, leaving the physiological model to be used only to correct for and measure pulmonary shunts corresponding to a particular disease state.
The low cost, affordable, accurate respired gas analysis technology that constitutes the basis of the present invention provides a mechanism for determining the concentrations of the constituents of a gas mixture by measurement of certain independent physical and/or thermodynamic properties such as density, viscosity, specific heat, dielectric constant, refractive index, electromagnetic radiation absorptivity, etc., of the mixture and determining the assay of the mixture that produces the measured values of the mixture properties. This technology, when applied to the measurement of cardiac output, offers significant cost and diagnostic advantages over other technologies that utilize the well-known and accepted Fick principle. For example, currently available non-invasive methods (e.g., the aforementioned NICO system) are limited to the use of only one indicator gas (carbon dioxide or oxygen) at a time. Since these gasses are products of metabolism or are themselves metabolized, the algorithms used are necessarily complex and not well validated because they must be able to accurately consider the metabolism process. By being able to use essentially inert (non-metabolizing) gasses, nitrogen and/or anesthetic gasses may be used as indicators and, moreover, the presence of more than one can be monitored simultaneously. This enables the clinician to select the indicator(s), or combinations thereof, appropriate to a particular clinical situation. For example, a denitrogenated patient on pure oxygen (and anesthetic gasses) in the operating room (OR) is a good candidate for a nitrogen indicator, whereas, a patient in the intensive care unit (ICU), who is breathing air or air and oxygen, may be a candidate for an anesthetic agent or another inert indicator such as helium. By choosing indicators that are not present in the body, the problem of accounting for residual indicator is eliminated. That is, one may account for all of the indicator injected as it is released and exhaled.
The above and still further objects, features and advantages of the present invention will become apparent upon consideration of the following definitions, descriptions and descriptive figures of specific embodiments thereof wherein like reference numerals in the various figures are utilized to designate like components. While these descriptions go into specific details of the invention, it should be understood that variations may and do exist and would be apparent to those skilled in the art based on the descriptions herein.